MMP8

MMP8
Available structures PDB Ortholog search:PDBeRCSB List of PDB id codes 1A86,1JAP,1I76,1ZVX,3TT4,2OY2,1ZS0,1JAN,1MMB,1I73,1A85,1KBC,1ZP5,1JH1,3DPF,1JAQ,3DPE,1BZS,4QKZ,1JAO,3DNG,2OY4,1MNC
Identifiers
Aliases	MMP8,CLG1, HNC, MMP-8, PMNL-CL, matrix metallopeptidase 8
External IDs	OMIM:120355;MGI:1202395;HomoloGene:22482;GeneCards:MMP8;OMA:MMP8 - orthologs
Gene location (Human) Chr. Chromosome 11 (human) Band 11q22.2 Start 102,711,796bp End 102,727,050bp
Gene location (Mouse) Chr. Chromosome 9 (mouse) Band 9|9 A1 Start 7,558,457bp End 7,568,486bp
RNA expressionpattern Bgee Human Mouse(ortholog) Top expressed in trabecular bone bone marrow bone marrow cells testicle monocyte blood amniotic fluid spleen granulocyte upper lobe of left lung Top expressed in granulocyte tibiofemoral joint muscle of thorax third toe bone marrow blood second toe cartilage tissue hallux bones of free part of lower limb More reference expression data BioGPS More reference expression data
Gene ontology Molecular function zinc ion binding peptidase activity hydrolase activity metallopeptidase activity metal ion binding serine-type endopeptidase activity metalloendopeptidase activity endopeptidase activity Cellular component extracellular matrix extracellular region specific granule lumen tertiary granule lumen extracellular space collagen-containing extracellular matrix Biological process collagen catabolic process extracellular matrix disassembly endodermal cell differentiation proteolysis neutrophil degranulation positive regulation of gene expression negative regulation of gene expression negative regulation of interleukin-10 production positive regulation of interleukin-6 production positive regulation of DNA binding positive regulation of MAPK cascade positive regulation of nitric oxide biosynthetic process positive regulation of JNK cascade regulation of neuroinflammatory response positive regulation of neuroinflammatory response positive regulation of NIK/NF-kappaB signaling positive regulation of reactive oxygen species biosynthetic process regulation of microglial cell activation positive regulation of microglial cell activation extracellular matrix organization Sources:Amigo/QuickGO
Orthologs Species Human Mouse Entrez 4317 17394 Ensembl ENSG00000118113 ENSMUSG00000005800 UniProt P22894 O70138 RefSeq (mRNA) NM_001304441 NM_001304442 NM_002424 NM_008611 RefSeq (protein) NP_001291370 NP_001291371 NP_002415 NP_032637 Location (UCSC) Chr 11: 102.71 – 102.73 Mb Chr 9: 7.56 – 7.57 Mb PubMedsearch
Wikidata
View/Edit Human View/Edit Mouse

Neutrophil collagenase,also known asmatrix metalloproteinase-8(MMP-8) or PMNL collagenase (MNL-CL), is acollagencleavingenzymewhich is present in the connective tissue of most mammals.In humans, the MMP-8proteinis encoded by theMMP8gene. The gene is part of a cluster of MMP genes which localize to chromosome 11q22.3.Most MMP's are secreted as inactive proproteins which are activated when cleaved by extracellular proteinases. However, the enzyme encoded by this gene is stored in secondary granules within neutrophils and is activated by autolytic cleavage.

Function

Proteins of thematrix metalloproteinase(MMP) family are involved in the breakdown ofextracellular matrixin normal physiological processes, such as embryonic development, reproduction, and tissue remodeling, as well as in disease processes, such as arthritis and metastasis. The primary function of MMP-8 is the degradation of type I, II and III collagens. In cancer, loss of MMP-8 in the murine MMTV-PyMT breast cancer model has been associated with increased tumor growth and metastatic burden, as well as enhanced tumor vascularity and altered immune cell infiltration.Furthermore, analysis of MMP-8 in breast cancer cell lines revealed a causal connection between MMP-8 activity and IL6 and IL8 production, suggesting a role for MMP-8 in the regulation of the innate immune system.

Further reading

• Chandler S, Miller KM, Clements JM, et al. (1997). "Matrix metalloproteinases, tumor necrosis factor and multiple sclerosis: an overview".J. Neuroimmunol.72(2): 155–61.doi:10.1016/S0165-5728(96)00179-8.PMID9042108.S2CID26495949.
• Massova I, Kotra LP, Fridman R, Mobashery S (1998). "Matrix metalloproteinases: structures, evolution, and diversification".FASEB J.12(25n26): 1075–95.CiteSeerX10.1.1.31.3959.doi:10.1142/S0217984998001256.PMID9737711.
• Nagase H, Woessner JF (1999)."Matrix metalloproteinases".J. Biol. Chem.274(31): 21491–4.doi:10.1074/jbc.274.31.21491.PMID10419448.
• Bläser J, Triebel S, Reinke H, Tschesche H (1992)."Formation of a covalent Hg-Cys-bond during mercurial activation of PMNL procollagenase gives evidence of a cysteine-switch mechanism".FEBS Lett.313(1): 59–61.Bibcode:1992FEBSL.313...59B.doi:10.1016/0014-5793(92)81184-N.PMID1330697.S2CID36829374.
• Devarajan P, Mookhtiar K, Van Wart H, Berliner N (1991)."Structure and expression of the cDNA encoding human neutrophil collagenase".Blood.77(12): 2731–8.doi:10.1182/blood.V77.12.2731.2731.PMID1646048.
• Bläser J, Knäuper V, Osthues A, et al. (1992)."Mercurial activation of human polymorphonuclear leucocyte procollagenase".Eur. J. Biochem.202(3): 1223–30.doi:10.1111/j.1432-1033.1991.tb16494.x.PMID1662606.
• Knäuper V, Krämer S, Reinke H, Tschesche H (1990)."Characterization and activation of procollagenase from human polymorphonuclear leucocytes. N-terminal sequence determination of the proenzyme and various proteolytically activated forms".Eur. J. Biochem.189(2): 295–300.doi:10.1111/j.1432-1033.1990.tb15489.x.PMID2159879.
• Hasty KA, Pourmotabbed TF, Goldberg GI, et al. (1990)."Human neutrophil collagenase. A distinct gene product with homology to other matrix metalloproteinases".J. Biol. Chem.265(20): 11421–4.doi:10.1016/S0021-9258(19)38413-3.PMID2164002.
• Knäuper V, Krämer S, Reinke H, Tschesche H (1990). "Partial amino acid sequence of human PMN leukocyte procollagenase".Biol. Chem. Hoppe-Seyler.371 Suppl: 295–304.PMID2169256.
• Knäuper V, Krämer S, Reinke H, Tschesche H (1990). "Partial amino-acid sequence of human PMN leukocyte procollagenase".Biol. Chem. Hoppe-Seyler.371(8): 733–734.doi:10.1515/bchm3.1990.371.2.733.PMID2169766.
• Mallya SK, Mookhtiar KA, Gao Y, et al. (1991). "Characterization of 58-kilodalton human neutrophil collagenase: comparison with human fibroblast collagenase".Biochemistry.29(47): 10628–34.doi:10.1021/bi00499a008.PMID2176876.
• Stams T, Spurlino JC, Smith DL, et al. (1995). "Structure of human neutrophil collagenase reveals large S1' specificity pocket".Nat. Struct. Biol.1(2): 119–23.doi:10.1038/nsb0294-119.PMID7656015.S2CID35458800.
• Fosang AJ, Last K, Neame PJ, et al. (1995)."Neutrophil collagenase (MMP-8) cleaves at the aggrecanase site E373-A374 in the interglobular domain of cartilage aggrecan".Biochem. J.304(2): 347–51.doi:10.1042/bj3040347.PMC1137499.PMID7998967.
• Bode W, Reinemer P, Huber R, et al. (1994)."The X-ray crystal structure of the catalytic domain of human neutrophil collagenase inhibited by a substrate analogue reveals the essentials for catalysis and specificity".EMBO J.13(6): 1263–9.doi:10.1002/j.1460-2075.1994.tb06378.x.PMC394940.PMID8137810.
• Fosang AJ, Last K, Knäuper V, et al. (1993)."Fibroblast and neutrophil collagenases cleave at two sites in the cartilage aggrecan interglobular domain".Biochem. J.295(1): 273–6.doi:10.1042/bj2950273.PMC1134849.PMID8216228.
• Reinemer P, Grams F, Huber R, et al. (1994)."Structural implications for the role of the N terminus in the 'superactivation' of collagenases. A crystallographic study".FEBS Lett.338(2): 227–33.Bibcode:1994FEBSL.338..227R.doi:10.1016/0014-5793(94)80370-6.PMID8307185.S2CID2454182.
• Thomas DB, Davies M, Peters JR, Williams JD (1993)."Tamm Horsfall protein binds to a single class of carbohydrate specific receptors on human neutrophils".Kidney Int.44(2): 423–9.doi:10.1038/ki.1993.260.PMID8397318.
• Cole AA, Chubinskaya S, Schumacher B, et al. (1996)."Chondrocyte matrix metalloproteinase-8. Human articular chondrocytes express neutrophil collagenase".J. Biol. Chem.271(18): 11023–6.doi:10.1074/jbc.271.18.11023.PMID8631924.
• Nakahara Y, Miyata T, Hamuro T, et al. (1996). "Amino acid sequence and carbohydrate structure of a recombinant human tissue factor pathway inhibitor expressed in Chinese hamster ovary cells: one N-and two O-linked carbohydrate chains are located between Kunitz domains 2 and 3 and one N-linked carbohydrate chain is in Kunitz domain 2".Biochemistry.35(20): 6450–9.doi:10.1021/bi9524880.PMID8639592.
• Pendás AM, Santamaría I, Alvarez MV, et al. (1997). "Fine physical mapping of the human matrix metalloproteinase genes clustered on chromosome 11q22.3".Genomics.37(2): 266–8.doi:10.1006/geno.1996.0557.PMID8921407.

External links

• TheMEROPSonline database for peptidases and their inhibitors:M10.002